Orit Pinhas-Hamiel1, Doreen Benary2, Kineret Mazor-Aronovich1, Michal Ben-Ami1, Yael Levy-Shraga1, Valentina Boyko3, Dalit Modan-Moses1, Liat Lerner-Geva4. 1. Pediatric Endocrinology and Diabetes Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel Sackler School of Medicine, Tel-Aviv University, Israel. 2. Pediatric Endocrinology and Diabetes Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel. 3. Women and Children's Health Research Unit, Gertner Institute. 4. Sackler School of Medicine, Tel-Aviv University, Israel Women and Children's Health Research Unit, Gertner Institute.
Abstract
OBJECTIVE: In obese children, bone age (BA) tends to significantly exceed chronological age (CA). In vitro studies in mice suggest that insulin may directly modulate skeletal growth. We investigated whether there is an association between fasting insulin and BA maturation in obese children. METHODS: The study cohort comprised 74 overweight and obese children ages 4 to 13 years. BA divided by CA was used as an index for bone advancement. Participants were classified into tertiles based on their BA:CA ratio. Advanced BA maturation was defined as the third tertile, with BA:CA > 1.21. Components of the metabolic syndrome, including fasting insulin, fasting glucose, triglycerides, and high-density lipoprotein (HDL) levels, were measured. RESULTS: Children with advanced BA were significantly younger, had a higher body mass index (BMI)-Z score (BMI-Z), and were taller than children with bone advancement in the lower tertiles. Females had a 4.7-fold increased risk for advanced BA compared with males (95% confidence interval [CI], 1.29-17.1; P = .02). Children with a BMI-Z ≥ 1.96 and fasting insulin ≤ 30 μU/L had a 3.6-fold increased risk of advanced BA (95% CI, 1.00-12.8; P = 0.05). Moreover, hyperinsulinemia (fasting insulin > 30 μU/L) was associated with a 6.8-fold increased risk for advanced BA, independent of the degree of obesity (95% CI, 1.45-32.1; P = .01). CONCLUSION: Marked hyperinsulinemia is associated with advanced BA in obese children. Insulin appears to modulate skeletal growth in humans.
OBJECTIVE: In obesechildren, bone age (BA) tends to significantly exceed chronological age (CA). In vitro studies in mice suggest that insulin may directly modulate skeletal growth. We investigated whether there is an association between fasting insulin and BA maturation in obesechildren. METHODS: The study cohort comprised 74 overweight and obesechildren ages 4 to 13 years. BA divided by CA was used as an index for bone advancement. Participants were classified into tertiles based on their BA:CA ratio. Advanced BA maturation was defined as the third tertile, with BA:CA > 1.21. Components of the metabolic syndrome, including fasting insulin, fasting glucose, triglycerides, and high-density lipoprotein (HDL) levels, were measured. RESULTS:Children with advanced BA were significantly younger, had a higher body mass index (BMI)-Z score (BMI-Z), and were taller than children with bone advancement in the lower tertiles. Females had a 4.7-fold increased risk for advanced BA compared with males (95% confidence interval [CI], 1.29-17.1; P = .02). Children with a BMI-Z ≥ 1.96 and fasting insulin ≤ 30 μU/L had a 3.6-fold increased risk of advanced BA (95% CI, 1.00-12.8; P = 0.05). Moreover, hyperinsulinemia (fasting insulin > 30 μU/L) was associated with a 6.8-fold increased risk for advanced BA, independent of the degree of obesity (95% CI, 1.45-32.1; P = .01). CONCLUSION: Marked hyperinsulinemia is associated with advanced BA in obesechildren. Insulin appears to modulate skeletal growth in humans.
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